合成路线:The methylation of 7-methoxy-1-tetralone (I) with methyl iodide and potassium tert-butoxide in THF gives the 2,2-dimethyl derivative (II),which is reduced with NaBH4 and acetylated with acetyl chloride yielding the acetate (III).The reduction of (III) with diethylborohydride in TFA affords 7-methoxy-2,2-dimethyltetraline (IV),which is submitted to a Birch reduction with Li/NH3 in THF affording 2,2-dimethyl-7-methoxy-1,2,3,4,5,8-hexahydronaphthalene (V).The condensation of (V) with homofarnesyl iodide (VI) by means of BuLi in THF gives intermediate (VII),which is treated with 2-sulfanylethanol and TFA yielding the ketone (VIII).The reaction of (VIII) with KHMDS and Tf2N-Ph in THF affords the enol triflate (IX),which is selectively brominated with N-bromosuccinimide (NBS) in THF giving the bromohydrine (X).The epoxidation of (X) with K2CO3 in methanol,followed by methylation with Me2CuLi in THF yields the epoxide (XI),which is treated with SiF4 and TFA to afford the fluoroketone (XII).The stereocontroled reduction of the ketone group of (XII) with a chiral oxaazaborolidine (OABL) gives the chiral alcohol (XIII),which is epoxidized by means of sodium isopropoxide in isopropanol yielding the chiral epoxide (XIV).
合成路线:The cyclization of (XIV) by means of MeAlCl2 in dichloromethane followed by benzoylation with benzoyl chloride gives a mixture of benzoates (XV) and (XVI) that are separated by chromatography.The desired isomer (XV) (additional (XV) is obtained by isomerization of (XVI) by HCl in hot acetic acid) was selctively methylenated with CH2I2 and Br2Zn in toluene yielding the cyclopropanated compound (XVII).Elimination of the benzoyl group of (XVII) with DIBAL in dichloromethane affords alcohol (XVIII),which is silylated with TBDMS-Cl and imidazole in DMF giving the silyl ether (XIX).The cleavage of the cyclopropane ring of (XIX) with tert-butyl perbenzoate,followed by hydrolysis of the resulting ester yields the methanol derivative (XX),which is selectively reduced with Li in THF/NH3 affording the cis-isomer (XXI).Finally,this compound is oxidized with NaClO4 in tert-butanol,and desilylated with tetrabutylammonium fluoride to give the target oleanolic acid.
参考文献标题:Enantioselective total synthesis of oleanolic acid,erythrodiol,beta-amyrin,and other pentacyclic triterpenes from a common intermediate
文献作者:Corey,E.J.; Lee,J.
参考来源:J Am Chem Soc 1993,1158873
产品链接: CAS No. 508-02-1››